Stable long-term cultures of self-renewing B cells and their applications

Immunol Rev. 2016 Mar;270(1):65-77. doi: 10.1111/imr.12395.

Abstract

Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen-presenting cells for the discovery of tumor neoantigens.

Keywords: B cells; BCL6; antibodies; germinal center; rabbit.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibody Formation / immunology
  • Antibody-Producing Cells / cytology
  • Antibody-Producing Cells / immunology*
  • Antibody-Producing Cells / metabolism*
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Self Renewal*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism
  • Drug Discovery
  • Gene Expression Regulation
  • Germinal Center / cytology
  • Germinal Center / physiology
  • Humans
  • Immunologic Memory
  • Interleukins / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • STAT3 Transcription Factor / metabolism
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction
  • Vaccines / immunology
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Antibodies, Monoclonal
  • Interleukins
  • Proto-Oncogene Proteins c-bcl-6
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Vaccines
  • bcl-X Protein
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase
  • interleukin-21